Go-alpha is a member of the family of guanine nucleotide binding (G) proteins which mediate signal transduction. Its function has not been fully elucidated. Different tissues have very different levels of Go-alpha protein with the highest levels being found in brain and neuroendocrine tissues. A preliminary study has shown high levels of Go-alpha in the serum from patients with a variety of neuroendocrine tumors but not in patients with other malignancies. We have cloned a human cDNA Go-alpha and have used this as a probe to evaluate the expression of Go-alpha mRNA in various malignancies by Northern blot analysis. Preliminary findings show increased levels of message in patients with malignancies of neuroendocrine origin (medullary thyroid carcinoma, pheochromocytoma, gastrinoma, glucagonoma and carcinoid) but not in other malignancies (e.g. squamous cell cancer of the lung, colon cancer and glioblastoma). Studies probing additional neuroendocrine and other malignancies both by Northern blot analysis and in situ hybridization, are ongoing in order to evaluate the value of Go-alpha as a marker for tumors of neuroendocrine origin. We hope to discover any possible role it might have in these malignancies. We have also evaluated the expression of various cytokines at the mRNA level in two human melanoma cell lines, since several immunomodulatory activities have been detected in the supernatants of melanoma cell lines. These factors may play a role in modulating the immune response to melanoma. One of the cell lines (WM-9) constitutively expressed mRNA for IL-1 alpha, GMCSF, and PDGF, whereas the other (KRFM-2) expressed GMCSF and PDGF but not IL-1 alpha. Neither cell line had IL-1 beta mRNA. Thus, there is heterogeneity in the expression of various cytokine mRNAs in melanoma cell lines. Further evaluation of the expression of various cytokine mRNAs is progress.